Exposure of adult rats to estradiol valerate induces ovarian cyst with early senescence of follicles.

Abstract

Environmental and therapeutic estrogens are known to play an important role in modulating the reproductive life and pubertal maturation in males as well as in females. Animal studies have shown that exogenously administered estrogen induces follicular cysts. However, the probable mechanisms underlying this abnormal ovarian development and its impact on steroidogenesis have been ill defined. The present study was therefore carried out to understand the ontogeny of ovarian pathology owing to adult estrogenisation. Regularly cycling female Holtzman rats were sacrificed at one week, two weeks, three weeks and four weeks after a subcutaneous administration of 2 mg of estradiol valerate (E(2)V). The effect of this supra-physiological estrogen on serum endocrine profiles, development of follicular cysts, follicular apoptosis and expression of markers of folliculogenesis viz., estrogen receptor (ER)-beta, inhibin A and progesterone receptor (PR) were studied. Results indicate a temporal augmentation of steroidogenesis, which was associated with induction of follicular cyst with theca cell hyperplasia and induction of apoptosis in the primary and secondary follicles of the ovaries. Immuno-histochemical localization showed an increase in inhibin A with a reduction in ER-beta and PR indicating early maturation, poor follicle growth and granulosa cell differentiation. Results indicate that exposure to exogenous estrogen in adulthood can have deleterious effects on the ovarian physiology and endocrinology which may ultimately lead to cystogenesis, loss of follicle pool and early senescence.

• Authors: Heena Shirwalkar, Deepak N Modi, Anurupa Maitra
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 272 Issue 1-2 Pg. 22-37 (Jun 30 2007) ISSN: 0303-7207 [Print] Ireland
• PMID: 17532555 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contraceptive Agents
• Gonadal Steroid Hormones
• Gonadotropins
• Estradiol

Topics

• Animals
• Apoptosis (drug effects)
• Cellular Senescence (drug effects)
• Contraceptive Agents (adverse effects, pharmacology)
• Corpus Luteum (drug effects)
• Estradiol (adverse effects, analogs & derivatives, pharmacology)
• Estrous Cycle (drug effects)
• Female
• Gene Expression Regulation (drug effects)
• Gonadal Steroid Hormones (blood)
• Gonadotropins (blood)
• Luteinization (drug effects)
• Ovarian Cysts (chemically induced, pathology)
• Ovarian Follicle (drug effects, growth & development, physiology)
• Ovary (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley